title: Virulence of H5N1 virus in mice attenuates after in vitro serial passages.
abstract: The virulence of A/Vietnam/1194/2004 (VN1194) in mice attenuated after serial passages in MDCK cells and chicken embryos, because the enriched large-plaque variants of the virus had significantly reduced virulence. In contrast, the small-plaque variants of the virus and the variants isolated from the brain of mice that were infected with the parental virus VN1194 had much higher virulence in mice. The virulence attenuation of serially propagated virus may be caused by the reduced neurotropism in mice. Our whole genome sequence analysis revealed substitutions of a total of two amino acids in PB1, three in PB2, two in PA common for virulence attenuated variants, all or part of which may be correlated with the virulence attenuation and reduced neurotropism of the serially propagated VN1194 in mice. Our study indicates that serial passages of VN1194 in vitro lead to adaptation and selection of variants that have markedly decreased virulence and neurotropism, which emphasizes the importance of direct analysis of original or less propagated virus samples.
authors.affiliation: State Key Laboratory of Pathogens and Bio-security, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Bohua
authors.initials: B
authors.lastname: Liu
authors.forename: Guohui
authors.initials: G
authors.lastname: Chang
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhan
authors.forename: Yukun
authors.initials: Y
authors.lastname: Xia
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Li
authors.forename: Yinhui
authors.initials: Y
authors.lastname: Yang
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001921:Brain / Q000821:virology; D002460:Cell Line; D004285:Dogs; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification / Q000472:pathogenicity*; D007251:Influenza, Human / Q000821:virology*; D051379:Mice; D012692:Serial Passage; D014764:Viral Proteins / Q000235:genetics; D014774:Virulence; D014776:Virus Cultivation; D014779:Virus Replication
chemical_list: D014764:Viral Proteins